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A novel suicide gene therapy for the treatment of p16-overexpressing tumors

Kohli, J., Campisi, J. & Demaria, M., Jan-2018, In : Oncotarget. 9, 7, p. 7274-7281 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

p16Ink4ais a potent cell cycle inhibitor engaged to support cell cycle arrest during cellular senescence. However, in tumors carrying mutations in key downstream effectors, p16Ink4ais highly expressed but fails to block cell proliferation. p16Ink4a-overexpressing tumor cells are highly aggressive and no targeted interventions are available. To study the effect of specific therapies, we generated murine sarcomas by overexpressing RAS oncogene and disrupting p53 activity. We observed that p16Ink4a-overxpressing murine sarcoma cells were resistant to ABT-263 and ABT-737, anti-cancer small molecules previously shown to eliminate p16Ink4a+senescent cells. We then generated sarcoma cells carrying a suicide and reporter gene, called 3MR, under the regulation of the full p16Ink4apromoter. Activation of the suicide efficiently killed p16Ink4a-overxpressing sarcoma cellsin vitroandin vivo. These data suggest that suicide gene therapy could represent an important therapeutic approach for the treatment of highly aggressive p16Ink4a+cancers.

Original languageEnglish
Pages (from-to)7274-7281
Number of pages8
JournalOncotarget
Volume9
Issue number7
Publication statusPublished - Jan-2018

    Keywords

  • Journal Article

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